Abstract |
The traditional Chinese medicinal mushroom, Ganoderma lucidum, has been used in Asia for several thousand years for the prevention and treatment of a variety of diseases, including cancer. In previous work, we purified ganoderic acid T (GA-T) from G. lucidum [28]. In the present study, we investigate the functions of GA-T in terms of its effects on invasion in vitro and metastasis in vivo. A trypan blue dye exclusion assay indicates that GA-T inhibits proliferation of HCT-116 cells, a human colon carcinoma cell line. Cell aggregation and adhesion assays show that GA-T promotes homotypic aggregation and simultaneously inhibits the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner.Wound healing assays indicate that GA-T also inhibits the migration of HCT-116 cells in a dose-dependent manner, and it suppresses the migration of 95-D cells, a highly metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition, GA-T inhibits the nuclear translocation of nuclear factor-kappaB ( NF-kappaB) and the degradation of inhibitor of kappaB-alpha ( IkappaBalpha), which leads to down-regulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Taken together, these results demonstrate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo, and thus it may act as a potential drug for treating cancer.
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Authors | Nian-Hong Chen, Jian-Wen Liu, Jian-Jiang Zhong |
Journal | Pharmacological reports : PR
(Pharmacol Rep)
2010 Jan-Feb
Vol. 62
Issue 1
Pg. 150-63
ISSN: 2299-5684 [Electronic] Switzerland |
PMID | 20360625
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibiotics, Antineoplastic
- Matrix Metalloproteinase Inhibitors
- Protease Inhibitors
- RNA, Neoplasm
- ganoderic acid T
- Lanosterol
- Matrix Metalloproteinases
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Antibiotics, Antineoplastic
(pharmacology)
- Blotting, Western
- Cell Adhesion
(drug effects)
- Cell Aggregation
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Dose-Response Relationship, Drug
- Humans
- Lanosterol
(analogs & derivatives, pharmacology)
- Male
- Matrix Metalloproteinase 9
(metabolism)
- Matrix Metalloproteinase Inhibitors
- Matrix Metalloproteinases
(biosynthesis)
- Mice
- Mice, Inbred C57BL
- Neoplasm Invasiveness
- Neoplasm Metastasis
(prevention & control)
- Protease Inhibitors
(pharmacology)
- RNA, Neoplasm
(biosynthesis)
- Reishi
(chemistry)
- Reverse Transcriptase Polymerase Chain Reaction
- Wound Healing
(drug effects)
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